JPH0542627B2 - - Google Patents

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention performs chemical analysis by spotting a certain amount of a sample liquid onto a chemical analysis slide (hereinafter also simply referred to as a slide) having a predetermined reagent layer. The present invention relates to a method for spotting a liquid sample in a chemical analyzer.

(Prior Art) Qualitative or quantitative analysis of specific chemical components in a liquid sample is a commonly performed operation in various industrial fields. In particular, quantitative analysis of chemical components or formed components in biological body fluids such as blood and urine is extremely important in the biochemical and clinical fields.

In recent years, dry-type slides have been developed that allow quantitative analysis of specific chemical components or organic components contained in a sample solution simply by applying small droplets of the sample solution. No. 21677, JP-A-55-164356, etc.) have been put into practical use. Using these slides allows sample liquid analysis to be performed more easily and quickly than conventional wet analysis methods, so their use is particularly important in medical institutions, laboratories, etc. that need to analyze a large number of samples. This is preferable.

In order to analyze the chemical components in a sample solution using such a slide, the sample solution is weighed and deposited on the slide, and then kept at a constant temperature for a predetermined period of time in an incubator (incubator). ) to cause a color reaction (dye-forming reaction), and then irradiate the slide with measurement irradiation light containing a wavelength pre-selected based on the combination of sample components and reagents contained in the reagent layer of the slide to detect its reflected light. This is used to measure the concentration, which allows quantitative analysis of the chemical components, etc. mentioned above.

When performing such an analysis, a predetermined amount of the sample liquid must be precisely measured and applied to the reagent layer of the slide. This is because if the amount of the sample liquid differs from the predetermined amount, the reflected optical density will differ and the analysis accuracy will also decrease. For this reason, various pipettes and the like have been devised so that a predetermined amount can be applied correctly when spotting and supplying a sample liquid. Such a pipette is designed, for example, by attaching a spotting tip to the tip of the pipette, aspirating a predetermined amount of sample liquid into the tip, and then spotting and dispensing this predetermined amount of sample liquid onto the reagent layer of the slide. There is something I did. In such a pipette,
Many use a piston-cylinder mechanism to suck a predetermined amount of sample liquid into the dotting tip and discharge it. To aspirate the sample liquid into the spotting tip and discharge it to the reagent layer using such a pipette, first insert the tip of the spotting tip into the sample liquid, and then use the piston-cylinder mechanism etc. Suction and hold a predetermined amount of sample liquid into the dotting tip, then position the tip of the dotting tip on the reagent layer of the slide,
The sample liquid in the spotting tip is dispensed onto the reagent layer using a piston-cylinder mechanism or the like.

(Problem to be Solved by the Invention) When the sample solution in the spotting tip is dispensed onto the reagent layer as described above, the sample solution is sucked into the spotting tip and is left in the air for a predetermined period of time. If left inside, the sample solution dries and the tip of the spotting tip becomes clogged, making spotting impossible. In particular, the amount of liquid to be spotted onto the reagent layer of a chemical analysis slide is small, and the opening at the tip of the spotting tip for sucking and discharging this liquid is small and easily clogged.

In this case, in the case of a disposable tip that only performs one spotting with one spotting tip, it is recommended to do the spotting immediately after aspirating the sample liquid to shorten the time that the tip is exposed to the air. It is easy to do this, but in the case of continuous spotting, in which multiple doses of sample solution are aspirated into a single spotting tip, and this is divided into multiple doses and spotted onto the reagent layer of multiple chemical analysis slides, the previous spotting tip and the time interval between the next dot and the next dot is likely to become large,
The above clogging problem is likely to occur.

(Means for Solving the Problems) For this reason, the present invention provides a method for sequentially spotting a plurality of chemical analysis slides using the same spotting tip in a chemical analyzer. The purpose of the present invention is to provide a liquid sample spotting method that does not cause clogging due to drying of the sample liquid at the tip of the spotting tip even if the time interval between spotting is long. This method is used.

With this spotting method, when spotting is performed on multiple chemical analysis slides using the same spotting tip, if the time interval from the previous spotting to the next spotting is less than a certain value, the previous spotting is completed. The next spotting is carried out using the same spotting tip, but if the above time interval is longer than a certain value, the tip of the spotting tip is immersed in the sample solution in the sample container and then waits after the previous spotting is completed. However, when starting the next spotting, the tip of the spotting tip is pulled out from the sample liquid, the sample liquid remaining in the spotting tip is discharged into the sample container, and then the tip is pulled out again. The tip of the tip is immersed in the sample solution, and a predetermined amount of sample solution is sucked and held from the tip into the spotting tip.
Next, the sample liquid in the spotting tip is spotted onto the reagent layer of the chemical analysis slide.

(Function) When using the above dotting method, if the time interval between dotting multiple times using the same dotting tip is short and no drying problem occurs, the dotting tip that completed the previous dotting can be used. Spotting is continued on the next chemical analysis slide, but if the time interval between spotting is large and the tip of the spotting tip becomes dry, the spotting is continued after the previous spotting is completed until the next spotting. By immersing the tip of the tip in the sample liquid and waiting, clogging due to drying of the sample liquid at the tip can be prevented, and when performing the next spotting, the sample liquid in the spotting tip is first discharged. By sucking the sample liquid into the spotting tip again, any remaining dried sample at the tip is removed. In addition, even if the air inside the suction/discharge mechanism expands or contracts due to temperature changes due to the increased spotting interval, these can be removed by discharging the sample liquid and then re-suctioning the sample liquid. influence can be eliminated.

(Example) Hereinafter, a specific method of the present invention will be described with reference to the drawings.

FIG. 1 is a perspective view showing an example of a chemical analyzer having an automatic spotting device 50 used for carrying out the spotting method according to the present invention, and FIG. 2 is a plan view with the cover plate 16 removed. The analyzer will be explained, and then the spotting method of the present invention in this chemical analyzer will be specifically explained.

The chemical analyzer has a cartridge 1 on the main body 10.
1. The incubator 20, the conveyance/insertion means 40, and the automatic spotting device 50 are attached, and further,
A display section 14 for displaying measurement data during measurement, operation keys 15 for operating the display, etc., and a magnetic disk insertion section 13 for recording are provided.

The cartridge 11 stores a plurality of unused chemical analysis slides 1 in a stack, and the slides 1 are
The pushing lever 12 pushes out the sheets one by one starting from the lowest one backward (in the direction of arrow A in FIG. 2).
In the incubator 20 located on the right side of the cartridge 11, a plurality of storage chambers 21 are formed to accommodate the slides 1, lined up on the right side on the same plane as the slide 1 at the lowest stage in the cartridge 11. A receiving tray 29 for receiving the used slide 1 discharged from the storage chamber 21 is disposed in front of the incubator 20, and a receiving tray 29 is arranged below to face the lower surface of the incubator 20 and to be slidable laterally (in the direction of arrow C). A read head (not shown) for reflective optical density measurements is provided.

Note that the reading head is the cartridge 11.
The cover slides to a position facing the slide 1 at the bottom of the incubator 20 and measures the reflective optical density of the slide 1 stored in each storage chamber 21 of the incubator 20, and measures the reflective optical density of the unused slide 1. Photometry will also be performed.

The incubator 20 has a built-in heater (not shown), and maintains the slide 1 held in the storage chamber 21 at a constant temperature (incubation).
The slide 1 consists of a dry multilayer film in which a support, a reagent layer, and a developing layer are laminated in this order in a frame with a circular hole for dropping a liquid sample, and a sample such as urine or blood is placed on this film. A predetermined amount of the solution is dropped, and the solution is kept at a constant temperature in the incubator 20 to cause a color reaction.

On the other hand, at the rear of the incubator 20, there is a section opposite to the inlet opening 21a of the storage chamber 21 in the lateral direction (arrow C).
A conveyance/insertion means 40 that is slidable in the direction) is disposed. This sliding movement is caused by the conveyance and
The insertion means 40 is driven by, for example, a linear motor, and is slidable to a position facing the cartridge 11 (the position indicated by the chain line X in FIG. 2). By this conveyance/insertion means 40,
Slide 1 pushed out from cartridge 11
The slide 1 is received by sliding it to the position indicated by the chain line X, and is transported to the position indicated by the solid line Y, which will be the spotting position described later, and then the slide 1 is inserted into a predetermined storage chamber 21. .

An automatic spotting device 50 equipped with a rotatable spotting arm 55 is disposed behind the conveyance/insertion means 40. A spotting tip 53 is detachably attached to the tip of this spotting arm 55, and this tip moves in the direction of arrow B in FIG. 2 and is positioned above the sample container 52 placed on the main body 10. the suction position (the position shown by the chain line in FIG. 2) and the spotting position (the position shown by the solid line in FIG. 2) located above the spotting hole 19 formed in the cover plate 16 on the main body 10. It is possible to move freely between the two.

Then, at the suction position, a predetermined amount of the sample liquid in the sample container 52 is sucked into the spotting tip 53.
Next, the dotting arm 55 is rotated to apply the dotting tip 5.
3 is positioned at the spotting position, a sample liquid is spotted and supplied onto the reagent layer of the slide 1 that is being transported to this spotting position. Thereafter, this slide 1 is inserted into the empty storage chamber 21 of the incubator 20 and incubated, and the optical reflection density at this time is read by a reading head to perform chemical analysis of the sample liquid. .

In order to implement the spotting method of the present invention, the automatic spotting device 50 needs to rotate and move the spotting tip 53 up and down, as well as suck and discharge the sample liquid into the spotting tip 53. The configuration will be explained based on FIG. That is, this spotting device 50 includes a tip vertical position control means 60 that moves the spotting arm 55 and the spotting tip 53 up and down, a container vertical position control means 70 that moves the sample container 52 up and down, and a device that rotates the spotting arm 55. Tip moving means 8 for moving the spotting tip 53 between the suction position and the spotting position
0. A suction/discharge means 90 that communicates with the chip 53 to suck the sample liquid into the chip 53 and discharge the sample liquid from the chip 53, and detects the liquid level position of the sample liquid in the sample container 52. A liquid level detection sensor 100 is provided.

The chip vertical position control means 60 includes a first pulse motor 61 attached to the main body 10, and a first pulse motor 61 attached to the main body 10.
A first drive body 63 connected to the rotating shaft of the pulse motor 61 via a coupling ring 62, and a male screw 6 that meshes with a female screw 63a formed on the first drive body 63.
4b. The first driven body 64 has a recess 64a that loosely fits into the protrusion 10a of the main body 10, as shown in FIG. Rotation is now blocked. Further, a rotating shaft 55a of a spotting arm 55 is connected to the upper part of the first driven body 64 so as to be able to rotate freely relative to each other. Therefore, the first pulse motor 6
1, when the first driving body 63 is rotated, since the first driven body 64 is prevented from rotating, the amount of screw engagement with the first driving body 63 changes, and the first driven body 64 is rotated.
is moved up and down, and at this time, the rotating shaft 55a of the spotting arm 55 connected to the first driven body 64 is also moved up and down.

The container vertical position control means 70 includes a second pulse motor 71 attached to the main body 10, a second drive body 73 connected to the rotating shaft of the second pulse motor 71 via a coupling 72, and a second drive body. 7
A male screw 74 that meshes with a female screw 73a formed in 3
b. The second driven body 74 has a recess 74a that loosely fits into the protrusion 10a of the main body 10, as shown in FIG. It has a mounting table 74c on which the sample container 52 is placed. Therefore, when the second drive body 73 is rotated by the second pulse motor 71, the second drive body 73 is rotated by the second pulse motor 71.
Since the driven body 74 is prevented from rotating, the amount of screw engagement with the second driving body 73 changes, and the second driven body 7
4 is moved up and down, and thereby the sample container 52 placed on the mounting table 74 is moved up and down.

The chip moving means 80 includes a rotary motor 81 attached to the main body 10, a drive gear 83 connected to the rotation shaft of the rotary motor 81 via a coupling ring 82, and a drive gear 83 that meshes with the drive gear 83. Driven gear 8 that can move up and down relative to 83
4, and the driven gear 84 is coaxially fixed to the rotating shaft 55a of the spotting arm 55. The rotation shaft 55a of the spotting arm 55 is rotatably supported by the main body 10. Therefore, when the rotation motor 81 is driven to rotate, this rotation is caused by the coupling 82, the drive gear 83, and the driven gear 84. Axis 5
This will be communicated to 5a. As a result, the spotting arm 55
is rotated around the rotating shaft 55a, and the spotting arm 5
A dotting tip 53 attached to the tip of the dot 5 can be moved between a suction position and a dotting position.

The suction/discharge means 90 includes a cam plate 92 on the rotating shaft.
a piston drive motor 91 having a piston drive motor 91; a piston rod 94 connected to the cam plate 92 via a link 93; a cylinder 95 into which a piston 94a attached to the tip of the piston rod 94 is fitted; It consists of a flexible hose 97 that connects a passage 98 that is formed and communicates with the space 53a in the dotting tip 53 with a space 96 in the cylinder 95. Piston drive motor 9
1 is converted into a reciprocating movement of the piston rod 94 by the link 93, and the resulting reciprocating movement of the piston 94a changes the volume of the cylinder interior space 96. The sample liquid is transmitted to the spotting tip internal space 53a, and the sample liquid is inhaled or discharged into the spotting tip internal space 53a.

The liquid level detection sensor 100 also includes a sample container 52.
It optically detects the liquid level position of the sample liquid in the sample container 5 using the container vertical position control means 70.
2 is moved up and down to detect the liquid level position.

Automatic spotting device 50 for a chemical analysis device as described above
The sample in the sample container 52 is spotted and supplied onto the reagent layer of the slide 1 at the spotting position, and this spotting is performed by each motor 61, 71, The operations of 81 and 91 are controlled automatically or manually as follows.

First, the container vertical position control means 70 moves the mounting table 74c up and down, and the liquid level detection sensor 100 detects the vertical position of the liquid level in the sample container 52.
Next, based on the detected liquid level position, the tip vertical position control means 60 is operated to move the dotting tip 53 attached to the dotting arm 55 in the suction position.
is moved downward, and the lower end of the spotting tip 53 is inserted into the sample liquid as shown by the two-dot chain line. Thereafter, the suction/discharge means 90 is activated to move the piston 94a to suck a predetermined amount of the sample liquid into the space 53a of the spotting tip 53. At this time, the liquid level drops by suctioning the sample liquid, so when this drop is detected by the liquid level detection sensor 100, the container vertical position control means 70 moves the mounting table 74c upward to remove the sample. The liquid level position of the container 52 may be kept constant.

As described above, the space 53 inside the spotting tip 53 is
When a specified amount of sample liquid is aspirated at point a, the spotting arm 55 is moved upward by the tip vertical position control means 60 to lift the spotting tip 53. Thereafter, the spotting arm 55 is moved to the rotating shaft 5 by the chip moving means 80.
5a to move the spotting tip 53 from the suction position to the spotting position. Next, when the spotting tip 53 is moved downward by the tip vertical position control means 60 and its tip is positioned near the upper part of the reagent layer portion 1a of the slide 1, the spotting tip 53 is placed by the action of the suction/discharge means 90. The sample liquid in the tip 53 is slowly discharged to form a liquid sphere at the lower end of the spotting tip 53 as shown in FIG. 6A. Then, the spotting tip 53 is lowered in this state to spot and supply the liquid sphere onto the reagent layer portion 1a of the slide 1 (see FIG. 6B). At this time, the distance "h" between the lower end of the spotting tip 53 and the surface of the reagent layer portion 1a is controlled to be always constant. Thereafter, the spotting tip 53 is moved upward to complete the first spotting of the sample liquid.

The spotting tip 53 can hold a plurality of sample liquids by suction, and when there are multiple analysis items, the spotting tip 53 can be held in the spotting position while holding multiple slides 1 with different reagent layers. Continuous spotting is carried out sequentially. In this continuous spotting, the spotted slide 1 at the spotting position is stored in a predetermined storage chamber 21 by the conveyance/insertion means 40, and the unspotted slide 1 is conveyed to the spotting position. and,
The spotting tip 53 is again moved down by the tip vertical position control means 60 on the unused slide 1 that has been transported to the spotting position, and the second sample liquid is applied onto the reagent layer of the chemical analysis slide 1. Perform dotting.

In this case, when the slide 1 is exchanged and transported quickly and the time interval between dots is short, the drying of the sample liquid at the tip of the dot spotting tip 53 exposed to the air is slight, resulting in clogging of the tip. However, for example, if there is no space in the storage chamber 21,
If it takes time to replace and convey the slide 1 and the time interval from the first spotting to the second spotting increases, the tip of the spotting tip 53 may become clogged due to drying of the sample liquid. may occur.

To prevent this drying, if it is known in advance that the time interval between the previous dotting and the next dotting is longer than a certain value, or if a predetermined time has elapsed, the previous dotting is completed. Rear tip moving means 8
0 to rotate the dotting arm 55 and move the dotting tip 53 to the suction position, the dotting tip 53 is moved by the tip up/down position control means 60 as shown by the two-dot chain line in FIG. Attach the tip to the sample container 52
immerse it in the sample solution inside and wait in this state.

When the slide 1 for the next spotting is carried out and the spotting is to be resumed, the spotting tip 53 in the standby state is first lifted above the sample liquid by the tip vertical position control means 60, and the spotting tip 53 in the standby state is lifted above the sample liquid, and the spotting tip 53 is aspirated. The sample liquid in the space 53a of the spotting tip 53 is completely discharged by the discharge means 90. After this, dotting tip 5
3 is lowered again to immerse its tip in the sample liquid, and the suction/discharge means 90 sucks a predetermined amount of the sample liquid into the space 53a of the spotting tip 53 again.

By doing this, even if a dried sample liquid adheres to the tip of the spotting tip 53, when the sample liquid in the spotting tip 53 is discharged, it is removed together with the discharged sample liquid, thereby preventing clogging. This effectively prevents Furthermore, due to changes in outside temperature between the previous dotting and the next dotting, the dotting tip 53 may
Even if the air in the space 53a, the space in the cylinder 95, or the passage 98 expands or contracts, the effect of the expansion or contraction can be eliminated by discharging the sample liquid and then reabsorbing it. This eliminates this problem and accurately controls the amount of suction and discharge.

Next, the automatic spotting device 50 is operated in the same manner as in the above case, and the sample liquid sucked into the space 53a of the spotting tip 53 is transferred onto the reagent layer of the unused slide 1 at the spotting position. Supply spot.

After that, this slide 1 is transferred to the transport/insertion means 40.
It is fed into a predetermined storage chamber 21 by the incubator 20 and kept at a constant temperature to cause a color reaction. The chemical analysis of the sample is performed by measuring the irradiation of light and its reflected optical density. When these measurements are completed, the slide 1 is discharged from the storage chamber 21 into the receiving tray 29 by the transport/insertion means 40. Hereinafter, by repeating the above operation, spotting can be performed multiple times using the same spotting tip 53 without clogging the tip of the spotting tip 53, and chemical analysis using a large number of chemical analysis slides can be performed automatically. Do it regularly and continuously.

(Effects of the Invention) As explained above, according to the present invention, even when spotting is performed multiple times using the same spotting tip and the spotting interval becomes larger than a certain value, the spotting tip is By immersing the tip of the tip in the sample liquid, drying and clogging of the sample liquid at the tip of the tip can be prevented. In addition, when performing the next spotting, the sample liquid in the spotting tip is discharged into the sample container and then re-suction is performed to remove the dried sample liquid remaining at the tip of the spotting tip. The influence of expansion and contraction of air in the suction/discharge mechanism can be eliminated, clogging does not occur, and the amount of suction/discharge can be accurately controlled.

[Brief explanation of the drawing]

Fig. 1 is a perspective view showing a chemical analyzer having an automatic spotting device used in the spotting method according to the present invention;
The figure is a plan view showing the chemical analysis device with the cover plate removed, and FIG. 3 is a schematic sectional view showing an example of an automatic spotting device used in the spotting method according to the present invention.
4 and 5 are sectional views taken along the arrows - and - in Fig. 3, and 6A and 6B are front sectional views showing the operation of spotting the sample liquid from the spotting tip onto the slide. It is. 10... Main body, 20... Incubator, 40
...Transportation/insertion means, 50...Automatic spotting device, 5
3... Spotting tip, 55... Spotting arm, 60...
...Tip vertical position control means, 70... Container vertical position control means, 80... Chip moving means, 90...
Suction/discharge means, 100...Liquid level detection sensor.

Claims (1)

[Scope of Claims] 1. The tip of a spotting tip is immersed in a sample liquid placed in a sample container, a predetermined amount of sample liquid is sucked and held from the tip into the spotting tip, and then the spotting tip is A liquid sample spotting method in which the same spotting tip is used to spot a plurality of chemical analysis slides in a chemical analyzer that performs chemical analysis by spotting a sample liquid in a spotting tip onto the reagent layer of a chemical analysis slide. When spotting on multiple chemical analysis slides, if the time interval from the previous spotting to the next spotting is less than a certain value, the spotting tip that completed the previous spotting is used for the next spotting. On the other hand, if the above-mentioned time interval is longer than a certain value, after the previous spotting is completed, the tip of the spotting tip is immersed in the sample liquid in the sample container and waits, and when starting the next spotting, , after pulling out the tip of the spotting tip from the sample liquid and discharging the sample liquid left in the spotting tip into the sample container, immerse the tip of the spotting tip in the sample liquid again. A chemical analysis device characterized in that a predetermined amount of sample liquid is sucked and held in the spotting tip from the tip thereof, and then the sample liquid in the spotting tip is spotted onto a reagent layer of a chemical analysis slide. Liquid sample spotting method.